Abstract
Purpose
Major clinical characteristics of BRCA1/2-related cancers include association with estrogen and metabolic consequences. We aimed to evaluate serum estradiol (E2) and insulin-like growth factor 1 (IGF-1) levels as a marker of insulin resistance in BRCA1/2 mutation carriers and high-risk, BRCA-negative controls.
Methods
Eligible cancer-free women (age 18–42 with regular menstrual cycles) who had been screened for BRCA1/2 mutations between 2005 and 2013 completed a questionnaire and underwent a single blood draw. E2 was measured with radioimmunoassay, and IGF-1 was measured with enzyme-linked immunosorbent assay.
Results
Eighty-six women participated (44 carriers and 42 non-carriers) in this study. BRCA mutation carriers were significantly younger than non-carriers (p = 0.0002). Age-adjusted basal (menstrual cycle days 2–5) serum E2 level was not significantly different between BRCA mutation carriers and non-carriers (30.4 vs. 24.7 pg/mL, p = 0.07). BRCA mutation carriers have significantly lower age-adjusted serum IGF-1 levels compared to non-carriers (89.7 vs. 112.6 ng/mL, p < 0.001). In women with BRCA mutations, the risk of having low serum IGF-1 level (IGF-1: ≤85 ng/mL) was 10.7 times as great as that of women without BRCA mutations (95 % CI 2.5, 46.2). There was a significant inverse association between basal E2 and IGF-1 levels in BRCA mutation carriers after adjusting age and BMI (p = 0.03).
Conclusions
IGF-1 level is significantly lower in cancer-free BRCA mutation carriers versus BRCA-negative controls, and there is a potential association between E2 and IGF-1 in cancer-free BRCA mutation carriers. Our findings may instigate future studies evaluating the role of both E2 and IGF-1 in BRCA mutation carriers.
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Acknowledgments
There are no financial disclosures from any authors. This study was supported by T90 grant from the Oncofertility Consortium (NIH 5TL1CA133837-05), Division of Reproductive Endocrinology and Infertility, University of North Carolina, a grant from the North Carolina Translational and Clinical Science Institute (2KR301104), Hettinger Foundation, a grant from the Penn Presbyterian Harrison Fund, Department of Obstetrics and Gynecology, University of Pennsylvania, and the NIH T32 Reproductive Epidemiology Training Grant (HD 007440).
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The authors declare that they have no conflict of interest.
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Kim, J., Johnson, L., Skrzynia, C. et al. Prospective multicenter cohort study of estrogen and insulin-like growth factor system in BRCA mutation carriers. Cancer Causes Control 26, 1087–1092 (2015). https://doi.org/10.1007/s10552-015-0601-9
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DOI: https://doi.org/10.1007/s10552-015-0601-9